Most cells in the normal adult human body do not divide. Cancer cells, however, escape growth regulation and divide unrestrained. To do this, they must replicate their chromosomes including the ends of these chromosomes, called telomeres.
Activation of the enzyme, telomerase, which adds telomeric sequence to chromosomal ends (reviewed in Collins, K., Curr. Opin Cell Biol. 12:378-383 (2000)) can overcome this senescence. See, Bodnar, A. G., et al., Science 279:349-352 (1998); reviewed in De Lange, T., Science 279:334-335 (1998)). Cell lines with active telomerase become immortalized. In vivo, previously senescent cells with active telomerase grow into tumors. Telomerase activity has been detected in essentially all major types of cancer (Shay, J. W. and Bacchetti, S., Eur. J. Cancer, 33:787-791 (1997); Cong, Y. S., et al., Microbiol. Mol. Biol. Rev. 66:407-425 (2002)). Hanahan and Weinberg have named the expression of the telomerase catalytic subunit as one of the six key events common to cancer (Cell 100: 57-70 (2000)). Expression of the genes coding for telomerase (TERT and TERC) has been proposed as a molecular marker for the diagnosis, monitoring, and prognosis of cancer.
However, not all tumors of a given cancer type contain detectable levels of telomerase activity. See, e.g., Shay, J. W. and Bacchetti, S. Eur. J. Cancer, 33:787-791 (1997); Yan, P. et al. Cancer Res. 59: 3166-3170 (1999). It is therefore important to identify molecular markers that identify tumors immortalized by a telomerase independent mechanism.